Skip to main content
SpringerLink
Log in

Vascular Endothelium in Health and Disease

  • Chapter
  • First Online:
Mechanisms of Vascular Disease

  • 1101 Accesses

Abstract

The vascular endothelium is a dynamic organ with secretory, synthetic, metabolic, and immunologic functions. Forming a continuous lining to every blood vessel in the body, endothelial cells play a key role in modulating vascular tone and permeability, angiogenesis, and in mediating haemostatic, inflammatory and reparative responses to local injury.

Advances in defining endothelial functions at the molecular level may lead to specific therapies to alleviate endothelial dysfunction associated with the progression of cardiovascular, chronic inflammatory and malignant diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aird WC. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012;2:1–13.

    Google Scholar 

  2. Marcu R, Choi YJ, Xue J, Fortin CL, Wang Y, Nagao RJ, et al. Human organ-specific endothelial cell heterogeneity. iScience. 2018;4:20–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Aird WC. Endothelium and haemostasis. Hamostaseologie. 2015;35:11–6.

    CAS  PubMed  Google Scholar 

  4. Garland CJ, Plane F, Kemp BK, Cocks TM. Endothelium-dependent hyperpolarization: a role in the control of vascular tone. Trends Pharmacol Sci. 1995;16:23–30.

    CAS  PubMed  Google Scholar 

  5. Yuan L, Chan GC, Beeler D, Janes L, Spokes KC, Dharaneeswaran H, et al. A role of stochastic phenotype switching in generating mosaic endothelial cell heterogeneity. Nat Commun. 2016;7:10160.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373–6.

    CAS  PubMed  Google Scholar 

  7. Gao Y. The multiple actions of NO. Pflugers Arch. 2010;459(6):829–39.

    CAS  PubMed  Google Scholar 

  8. Keravis T, Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br J Pharmacol. 2012;165:1288–305.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Lima B, Forrester MT, Hess DT, Stamler JS. S-nitrosylation in cardiovascular signaling. Circ Res. 2010;106:633–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Mayer B, Hemmens B. Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci. 1997;22:477–81.

    CAS  PubMed  Google Scholar 

  11. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33:829–37.

    PubMed  Google Scholar 

  12. García-Cardeña G, Martasek P, Masters BSS, Skidd PM, Couet J, Li S, et al. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the NOS caveolin binding domain in vivo. J Biol Chem. 1997;272:25437–40.

    PubMed  Google Scholar 

  13. Park S, Sorenson CM, Sheibani N. PECAM-1 isoforms, eNOS and endoglin axis in regulation of angiogenesis. Clin Sci. 2015;129:217–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Green DJ, O’Driscoll G, Blanksby BA, Taylor RR. Control of skeletal muscle blood flow during dynamic exercise: contribution of endothelium-derived nitric oxide. Sports Med. 1996;21:119–46.

    CAS  PubMed  Google Scholar 

  15. Shimokawa H, Aarhus LL, Vanhoutte PM. Porcine coronary arteries with regenerated endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res. 1987;61:256–70.

    CAS  PubMed  Google Scholar 

  16. Willeit P, Freitag DF, Laukkanen JA, Chowdhury S, Gobin R, Mayr M, et al. Asymmetric dimethylarginine and cardiovascular risk: systematic review and meta-analysis of 22 prospective studies. J Am Heart Assoc. 2015;4:e001833.

    PubMed  PubMed Central  Google Scholar 

  17. Vanhoutte PM, Shimokawa H, Feletou M, Tang EHC. Endothelial dysfunction and vascular disease—a 30th anniversary update. Acta Physiol. 2017;219:22–96.

    CAS  Google Scholar 

  18. Leffler CW, Parfenova H, Jaggar JH, Wang R. Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. J Appl Physiol. 2006;100:1065–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase. Science. 2008;322:587–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Olson KR. Hydrogen sulfide as an oxygen sensor. Clin Chem Lab Med. 2013;51:623–32.

    CAS  PubMed  Google Scholar 

  21. Ono K, Akaike T, Sawa T, Kumagai Y, Wink DA, Tantillo DJ, et al. Redox chemistry and chemical biology of H2S, hydropersulfides, and derived species: implications of their possible biological activity and utility. Free Radic Biol Med. 2014;77:82–94.

    CAS  PubMed  Google Scholar 

  22. Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, et al. Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res. 2011;109:1259–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Tang G, Yang G, Jiang B, Ju Y, Wu L, Wang R. H2S is an endothelium-derived hyperpolarizing factor. Antioxid Redox Signal. 2013;19:1634–46.

    CAS  PubMed  Google Scholar 

  24. Wang R, Szabo C, Ichinose F, Ahmed A, Whiteman M, Papapetropoulos A. The role of H2S bioavailability in endothelial dysfunction. Trends Pharmacol Sci. 2015;36:568–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Edwards G, Félétou M, Weston AH. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflügers Arch. 2010;459:863–79.

    CAS  PubMed  Google Scholar 

  26. Kerr PM, Wei R, Tam R, Sandow SL, Murphy TV, Ondrusova K, et al. Activation of endothelial IKCa channels underlies NO-dependent myoendothelial feedback. Vasc Pharmacol. 2015;74:130–8.

    CAS  Google Scholar 

  27. Kerr PM, Tam R, Narang D, Potts K, McMillan D, McMillan K, et al. Endothelial calcium-activated potassium channels as therapeutic targets to enhance availability of nitric oxide. Can J Physiol Pharmacol. 2012;90:739–52.

    CAS  PubMed  Google Scholar 

  28. Félétou M, Huang Y, Vanhoutte PM. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br J Pharmacol. 2011;164:894–912.

    PubMed  PubMed Central  Google Scholar 

  29. Patrono C. Cardiovascular effects of cyclooxygenase-2 inhibitors: a mechanistic and clinical perspective. Br J Clin Pharmacol. 2016;82:957–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Yang L, Mäki-Petäjä K, Cheriyan J, McEniery C, Wilkinson IB. The role of epoxyeicosatrienoic acids in the cardiovascular system. Br J Clin Pharmacol. 2015;80:28–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Park SK, Herrnreiter A, Pfister SL, Gauthier KM, Falck BA, Falck JR, et al. GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells. J Biol Chem. 2018;293:10675–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Campbell WB, Imig JD, Schmitz JM, Falck JR. Orally active epoxyeicosatrienoic acid analogs. J Cardiovasc Pharmacol. 2017;70:211–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A. 1989;86:2863–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Maguire JJ, Davenport AP. Endothelin@25—new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR review 12. Br J Pharmacol. 2014;171:5555–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Félétou M, Köhler R, Vanhoutte PM. Nitric oxide: orchestrator of endothelium-dependent responses. Ann Med. 2012;44:694–716.

    PubMed  Google Scholar 

  36. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932–6.

    CAS  PubMed  Google Scholar 

  37. Ucuzian AA, Gassman AA, East AT, Greisler HP. Molecular mediators of angiogenesis. J Burn Care Res. 2010;31:158–75.

    PubMed  PubMed Central  Google Scholar 

  38. Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007;100:782–94.

    CAS  PubMed  Google Scholar 

  39. Rey S, Semenza GL. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res. 2010;86:236–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Zimna A, Kurpisz M. Hypoxia-Inducible factor-1 in physiological and pathophysiological angiogenesis: applications and therapies. Biomed Res Int. 2015;2015:549412.

    PubMed  PubMed Central  Google Scholar 

  41. Pearson JD. Endothelial progenitor cells—an evolving story. Microvasc Res. 2010;79:162–8.

    CAS  PubMed  Google Scholar 

  42. Asahara T, Murohara T, Sullivan A, Sliver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–7.

    CAS  PubMed  Google Scholar 

  43. Tongers J, Roncalli JG, Losordo DW. Role of endothelial progenitor cells during ischemia-induced vasculogenesis and collateral formation. Microvasc Res. 2010;79:200–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. van Hinsbergh VWM. Endothelium—role in regulation of coagulation and inflammation. Semin Immunopathol. 2012;34:93–106.

    PubMed  Google Scholar 

  45. Kazmi SSH, Jørgensen JJ, Sundhagen JO, Krog AH, Flørenes TL, Kollerøs D, et al. A comparative cohort study of totally laparoscopic and open aortobifemoral bypass for the treatment of advanced atherosclerosis. Vasc Health Risk Manag. 2015;11:541–7.

    PubMed  PubMed Central  Google Scholar 

  46. Muller WA. Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol. 2011;6:323–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Chistiakov DA, Bobryshev YV, Kozarov E, Sobenin IA, Orekhov AN. Role of gut microbiota in the modulation of atherosclerosis-associated immune response. Front Microbiol. 2015;6:671.

    PubMed  PubMed Central  Google Scholar 

Further Reading

  • Aird WC. Endothelium and haemostasis. Hamostaseologie. 2015;35:11–6.

    CAS  PubMed  Google Scholar 

  • Chatterjee S. Endothelial mechanotransduction, redox signaling and the regulation of vascular inflammatory pathways. Front Physiol. 2018;7:524.

    Google Scholar 

  • Maruhashi T, Kihara Y, Higashi Y. Assessment of endothelium-independent vasodilation: from methodology to clinical perspectives. J Hypertens. 2018;36:1460–7.

    CAS  PubMed  Google Scholar 

  • Vanhoutte PM. Nitric oxide: from good to bad. Ann Vasc Dis. 2018;11:41–51.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Alberta, Edmonton, AB, Canada

    Ran Wei, Stephen L. Gust, Raymond Tam & Frances Plane

  2. Faculty of Nursing, Robbins Health Learning Centre, MacEwan University, Edmonton, AB, Canada

    Paul M. Kerr

Authors
  1. Ran Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul M. Kerr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen L. Gust
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Raymond Tam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Frances Plane
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frances Plane .

Editor information

Editors and Affiliations

  1. Discipline of Surgery, The University of Adelaide, Adelaide, SA, Australia

    Robert Fitridge

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wei, R., Kerr, P.M., Gust, S.L., Tam, R., Plane, F. (2020). Vascular Endothelium in Health and Disease. In: Fitridge, R. (eds) Mechanisms of Vascular Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-43683-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-43683-4_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-43682-7

  • Online ISBN: 978-3-030-43683-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation